Heart disease is the leading cause of death for both men and women in the United States. In 2006, 631,636 people died of heart disease and heart disease caused 26% of deaths—more than one in every four—in the United States. Every year, about 785,000 Americans have a first heart attack and other 470,000 Americans who already had one or more heart attacks have another attack. Coronary heart disease is the most common type of heart disease. In 2005, 445,687 people died from coronary heart disease and these numbers are on the rise. According to 2010 statistics, 1 in 3 Americans (36.9%) have some form of heart disease, including high blood pressure, coronary heart disease, heart failure, stroke, and other conditions. By 2030, approximately 116 million people in the United States (40.5%) will have some form of cardiovascular disease.
Between 2010-30, it is projected that the cost of medical care for heart disease (in 2008 dollar values) will rise from $273 billion to $818 billion, according to an American Heart Association policy statement published in Circulation: Journal of the American Heart Association. See Heidenreich P A, et al. Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association Circulation (2011).
The coronary angiogram, also referred to as the catheterization examination, is regarded as the “gold standard” for diagnosis of coronary artery disease (CAD). However, the use of coronary angiograms expose over 2.7 million Medicare/Medicaid reimbursed Americans to the risks and result in costs of invasive diagnostic examination every year, whereas only about 61% of these patients require clinical intervention. See Patel M R et al., Low diagnostic yield of elective coronary angiography, N Engl J. Med. 2010 March 11; 362(10):886-95 (erratum as published at N Engl J Med. 2010 July 29; 363(5):498).
Preliminary diagnosis of CAD is commonly performed using radiology imaging modalities such as contrast Dobutamine Stress Echocardiography (DSE), nuclear cardiology Single Photon Emission Computed Tomography (SPECT) and Cardiac Computed Tomography (Cardiac CT). While DSE primarily assesses wall motion, SPECT allows simultaneous determination of myocardial perfusion and wall motion at relatively low resolution, although it exposes the patient to ionizing radiation and does not offer the opportunity to distinguish between wall-thickening function and perfusion.
The current landscape of diagnostic tests for heart disease creates a need to implement a less expensive screening test with high negative predictive value in order to be the gate-keeper to an invasive examination or an interventional surgery and also to augment the decision making capability of the clinician for patients with low and medium Framingham risk scores. In turn, this facilitates improved healthcare for the individual patient and at significant healthcare cost savings for the population. First-pass perfusion image acquisitions from cardiac magnetic resonance imaging (CMR) is a low cost, no toxicity, high sensitivity, and high specificity imaging modality for cardiac perfusion diagnostics which has the potential to solve this problem.
CMR is a currently underutilized capital equipment with great untapped clinical potential, according to a clinically proven comparison of CMR with other imaging modalities, which has indicated higher sensitivity and specificity in detection of coronary artery disease compared with SPECT. See Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial, Lancet, 2012 Feb. 4; 379(9814):453-60.
A recent survey of cardiologists in the American Heart Journal has indicated that most cardiologists were willing to enroll patients with at least moderate ischemia into a trial using initial non-invasive diagnosis in preference to advancing directly to invasive cardiac catheterization. When added to the recent prognostic data that a normal (AIR stress test provides, namely, <1% mortality at 3 years as shown in 1500 consecutive patients, this is a compelling cost-effective strategy which does not involve the use of cardiac catheterization or a nuclear laboratory. Accordingly, the use of CMR may avert unnecessary catheterizations by assessment of cardiac perfusion and function using CMR.
Thus, CMR is an appropriate “gate-keeper” to the catheterization laboratory which will provide the clinician with assistance in detecting perfusion abnormalities which may indicate a problem with a patient's cardiac health. Further, CMR may be used to assist the clinician in detecting, at an early stage, perfusion abnormalities which may indicate a problem with a patient's cardiac health. Accordingly, the use of CMR may save several millions of dollars in cardiology related hospitalization and interventional treatment; effectively curbing the $273 billion cost of medical care for heart disease in the US. In addition, the American College of Cardiology (ACC) and American Heart Association guidelines recognize CMR as the “gold standard” for a large and growing number of cardiac applications.
CMR is a versatile non-invasive and non-ionizing imaging modality and offers time resolved image data to evaluate cardiac function at rest and either vasolidation or pharmacological stress, allowing myocardial perfusion to be evaluated independently of wall-thickening function. There is a need in the art for a program to efficiently and economically disseminate this non-invasive, non-radioactive, and safe CMR technique, which would have obvious advantages to the community.
Gadolinium-diethyenetriaminepentaacetate, a non-nephrotoxic extravascular contrast agent, is used to increase T1 weighted tissue signal from the myocardium CMR imaging. Modern CMR scanners use pulse sequences capable of fast image acquisition to obtain temporally resolved short-axis multi-slice first-pass perfusion image acquisitions of the heart. Such contrast enhanced first-pass perfusion CMR can be repeated regularly without any adverse effects for the patient. See N. M. Wilke, et al., “Magnetic resonance first-pass myocardial perfusion imaging: clinical validation and future applications,” J Magn Reson Imaging, vol. 10, pp. 676-85, November 1999. Time resolved perfusion imaging is important because it provides crucial information, aiding identification of a stress response which is not possible to obtain from traditional imaging modalities. Based on M. Doyle, et al., “The impact of myocardial flow reserve on the detection of coronary artery disease by perfusion imaging methods: an NHLBI WISE study,” J Cardiovasc Magn Reson, vol. 5, pp. 475-85, July 2003, there is evidence to show that CMR is the only modality with the sensitivity to identify the extent of the vasodilatory response. They showed that non-time resolved nuclear SPECT imaging lost accuracy when the vasodilatory response was inadequate (affecting about 30% of patients), but that knowledge of the vasodilatory response could be incorporated to improve the detection of myocardium at risk using first pass contrast perfusion CMR.
However, the transient image data in first-pass contrast perfusion sequences contain a high amount of dynamic information and pixel-level or voxel-level noise, making it difficult to evaluate visually without quantification. Further, quantification of myocardial perfusion is known to be challenging. See J. U. Fluckiger, et al., “Constrained estimation of the arterial input function for myocardial perfusion cardiovascular magnetic resonance,” Magn Reson Med, Mar. 28, 2011. The method as described is capable of quantifying image data from perfusion sequences and subsequently providing a spatial map of perfusion conditions using physical contrast agent transport properties i.e. advection and diffusion. Previously, M. Doyle, et al., “Prognostic value of global MR myocardial perfusion imaging in women with suspected myocardial ischemia and no obstructive coronary disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study,” JACC Cardiovasc Imaging, vol. 3, pp. 1030-6, October 2010, showed that quantitative CMR perfusion is capable of detecting global (as opposed to regional) perfusion abnormalities which are unlikely to be seen in infarct imaging methods such as late Gadolinium enhancement CMR or on a coronary angiogram, possibly due to the small caliber of the arteries involved, which may represent an early stenosis condition prior to occlusion of the epicardial coronary arteries. Early diagnosis of suspected myocardial ischemia allow better patient management and prevention of progression to myocardial infarction and early cardiovascular death.